Flanagan, Christie A.

Abstract Background: The Alaska Tribal Health System is working to increase colorectal cancer (CRC) screening among Alaska Native peoples. It is unknown why people who initially agree to screening might not follow through to complete their screening. Methods: As part of a larger intervention investigating multi-target stool DNA (mt-sDNA) test use in rural Alaska communities, we interviewed Alaska Native people who had agreed to scheduling a colonoscopy or having a mt-sDNA kit sent to their home but who did not complete their selected test. Results: Of 531 Alaska Native people who initially agreed but did not complete screening, 299 (56%) were able to be contacted for a follow-up survey. Of those, 256 (86%) answered the survey; 187/224 (83%) who had chosen mt-sDNA, and 69/75 (93%) who had chosen colonoscopy. Reported reasons for non-completion of stool DNA test kits included being busy or forgetting, being uncomfortable doing a stool test, and not knowing how to do the test or concerns over how to return the kit for processing. Reasons for non-completion of colonoscopy included scheduling issues, physical health issues, travel, and housing barriers, as well as cost, fear, and being too busy. Of note, many respondents in both groups indicated they would still be interested in CRC screening in the future or were currently pursuing screening. Conclusions: This was the first exploration of reasons for non-adherence to CRC screening after initial test request by Alaska Native people. Many of the identified themes are amenable to health care system changes for future interventions to improve screening outreach and uptake. Citation Format: Diana Redwood, Christie A. Flanagan, Lauren Jeffries, Melissa Toffolon, Joseph Klejka, Lila J. Finney Rutten, Judith S. Kaur, John B. Kisiel. Non-completion of colorectal cancer screening among Alaska Native people in an intervention trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2474.

Cigarette smoking is associated with numerous adverse pregnancy outcomes, due in part to polycyclic aromatic hydrocarbons and free radicals produced by combustion. Less is known about the impact of smokeless tobacco (ST) use during pregnancy. Alaska Native women report higher rates of cigarette and ST use during pregnancy than non-Native women. We investigated oxidative stress and hypoxia pathways in term placentae from Alaska Native women who did (commercial or iqmik; n = 10) or did not ( n = 18) use ST during pregnancy. Despite substantial maternal exposure to nicotine, placentae of women who used ST had similar mRNA levels of antioxidant enzymes and markers of hypoxia compared to those who did not use tobacco. Although mRNA levels of angiogenesis markers vegf and vegfr2 were similar between groups, vegfr1 mRNA levels are increased in placentae of women using ST compared to women who did not use tobacco. Together these results suggest that, while ST use may not have as significant an effect on oxidative stress pathways in the placenta as cigarette smoking, an effect is present. It is not clear what this limited effect may have on the developing fetus.

Abstract Background: Alaska Native people are committed to increasing colorectal cancer (CRC) screening to reduce the high rate of CRC in this population. We conducted a community-level cluster randomized controlled trial (RCT) to evaluate the impact of multi-target stool DNA test introduction (mt-sDNA; Cologuard® Exact Sciences, Madison WI) on CRC screening in southwest Alaska Native communities using a mt-sDNA pre-processing lab in Anchorage, Alaska. Methods: A total of 32 rural/remote Alaska Native communities were evenly randomized to either high intensity patient navigation or medium intensity mailed health education compared to 14 communities receiving standard of care (screening recommendations at health care visits). The intervention was conducted from April 2021-February 2023. Outcome measures included CRC screening completion within 12 months and method used (mt-sDNA vs colonoscopy). Results: A total of 2032 Alaska Native participants (mean [SD] age, 56 [8.4] years; 817 women [40%]) were enrolled: 587 participants randomized to usual care, 696 participants randomized to the mailed education arm, and 749 participants randomized to the patient navigation arm. The mt-sDNA test was significantly preferred over colonoscopy by both mailed education participants (68%) and patient navigation participants (71%) (p<0.01). Mt-sDNA was somewhat more preferred by older participants ages 65-75 (79%) vs younger participants ages 45-54 (64%). Both men (71%) and women (68%) significantly preferred mt-sDNA compared with colonoscopy (p<0.01). Overall, 38% of those in the patient navigation intervention completed screening compared with 33% in the mailed education intervention and 10% in the usual care arm. No significant differences were observed in mt-sDNA completion between the patient navigation arm (154 participants [40%]) and the mailed education arm (100 participants [36%]) (p= 0.34). Colonoscopy completion (not including follow-up colonoscopies after abnormal stool tests) was higher in both the patient navigation arm (112 participants [44%]) and the mailed education arm (87 participants [43%]) compared with usual care (38 participants [14%]). Over 61% of kits sent to participants were completed and returned, however, 38% of the kits were not able to be processed, primarily because of mail transit time exceeding the manufacturer’s collection-to-processing limitation of 72 hrs. Conclusions: In this RCT among Alaska Native peoples who were not up to date with CRC screening recommendations, both a mailed education intervention and a patient navigator facilitated intervention were effective at increasing CRC screening compared with usual care. Participants overwhelmingly preferred mt-sDNA for screening but limitations in getting samples to the lab in time for analysis meant that about one-third of mt-sDNA samples were unable to be processed. These findings show that screening outreach and mt-sDNA use can substantially increase CRC screening, but shipping and weather issues remain to be addressed for expanding use of mt-sDNA in rural/remote Alaskan communities. Citation Format: Diana Redwood, Christie Flanagan, Lauren Jeffries, Peter Holck, Danika Bailie, Christine Desnoyers, Joseph Klejka, Lila Rutten, John Kisiel. Increase in colorectal cancer screening among rural and remote Alaska Native peoples using the multi-target stool DNA: A randomized controlled trial [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A148.

Abstract Purpose We examined barriers and facilitators to colorectal cancer (CRC) screening among Alaska Native individuals who had never been screened or were not up to date with screening guidelines. Methods As part of a larger study investigating the use of the multitarget stool DNA test in rural Alaska communities, we conducted focus groups and in‐depth interviews with 28 never screened or not up‐to‐date Alaska Native people in two remote communities between November 2022 and July 2023. Participants shared their barriers to CRC screening and offered suggestions to improve programs to better reach those who are guideline discordant. Findings General screening barriers included lack of knowledge, fear of discovering you have cancer, and cultural health beliefs. Colonoscopy‐specific barriers included embarrassment from knowing the local medical staff, having rectal area viewed or touched, fear of pain and injury, difficulty scheduling a procedure due to traditional food gathering activities, lack of provider referrals/reminders, and the high cost of air travel required to get to a colonoscopy facility. Stool DNA‐specific concerns included not feeling that it was as good as colonoscopy, lack of privacy to do the test, and hesitancy collecting stool samples. Suggestions for increasing screening rates included increasing access via paid air transportation, using local indigenous languages, improving provider relationships and reminder systems, and providing CRC and screening education using trusted messengers. Conclusions This was the first exploration of the perceptions of CRC screening among guideline discordant Alaska Native people. Identified themes can be used to improve screening program outreach effectiveness in the future.

The Alaska Tribal Health System is increasing colorectal cancer (CRC) screening among Alaska Native (AN) peoples, who experience the highest CRC rate in the world. Through a clinical trial (NCT04336397), AN people living in rural/remote Alaska were offered either the previously unavailable multi-target stool DNA test (mt-sDNA; Cologuard®) or colonoscopy. From April 2022 to August 2024, 113 (59%) people who completed mt-sDNA testing and 51 (39%) who completed a colonoscopy procedure participated in a survey on factors influencing their screening test choice. The majority of mt-sDNA participants (79%) were aware of the colonoscopy option, while most colonoscopy participants (72%) reported being unaware of the mt-sDNA option. Key mt-sDNA preference themes included not having to travel, less time commitment, childcare and work responsibilities, physical limitations, greater convenience, and the test being less invasive and dangerous than a colonoscopy. In contrast, colonoscopy preference themes included wanting to adhere to screening recommendations, be proactive about preventative health, family history of cancer, awareness of the higher CRC risk among AN peoples, as well as the belief that colonoscopy is more reliable and accurate since it is performed by medical providers. These findings underscore the complex factors influencing CRC screening preferences among rural and remote AN people. Limited access to medical facilities, financial burdens, and personal commitments, along with personal factors, have a substantial bearing on the screening decision-making process. Recognizing and addressing these multifaceted influences can help CRC screening programs better meet community member needs and preferences, ultimately improving screening rates and colorectal health outcomes.

The Alaska Tribal Health System is working to increase colorectal cancer (CRC) screening among Alaska Native people, who experience the highest CRC rates in the world. This study examined CRC screening provider- and system-level barriers and facilitators from the perspective of healthcare providers serving Alaska Native people in rural/remote communities. A total of 28 provider (physicians, advanced practice, and Community Health Aides/Practitioners) interviews were held from 1 February to 30 November 2021. Colonoscopy provider-level barrier themes included time, competing priorities, and staffing, while system-level barriers included travel costs, weather, and the COVID-19 pandemic. Multi-target stool DNA (mt-sDNA) barrier themes included test viability and unfamiliarity, and previous stool tests experiences. For both tests, limited medical record reminders was a major barrier. Facilitator themes for both tests included community outreach, cultural competency and patient navigation, and clinic/system improvements. In-depth interviews with tribal health providers showed that adding mt-sDNA testing may help address system-level colonoscopy barriers such as waitlists and travel costs, but other barriers remain. Further research is needed into patient barriers and facilitators, as well as the effectiveness of integrating mt-sDNA into a geographically dispersed tribal health system to reduce cancer disparities and build equity in CRC prevention among Alaska Native people.

Prenatal tobacco use among Alaska Native (AN) women has decreased substantially over the past two decades. Previous research suggests that providing AN women with feedback regarding fetal exposure to tobacco may further promote cessation. Transporters in the placenta regulate fetal exposure to nutrients and xenobiotics, including compounds associated with tobacco use. We examined whether prenatal tobacco use impacts transporter expression in the placenta, and whether this is influenced by fetal sex, degree of tobacco exposure, or transporter genotype. At delivery, we obtained placental samples from AN research participants who smoked cigarettes, used commercial chew or iqmik (oral tobacco), or did not use tobacco during pregnancy. Transporter expression was evaluated using qRT‐PCR and Western blotting and tested for correlations between transcript levels and urinary biomarkers of tobacco use. The impact of BCRP/ABCG2 and OATP2B1/SLCO2B1 genotypes on protein expression was also examined. Oral tobacco use was associated with decreased P‐gp and increased MRP1, MRP3, LAT1, and PMAT mRNA expression. Transcript levels of multiple transporters significantly correlated with tobacco biomarkers in maternal and fetal urine. In women carrying male fetuses, both smoking and oral tobacco were associated with decreased P‐gp. Oral tobacco was also associated with decreased LAT1 in women carrying female fetuses. BCRP and OATP2B1 genotypes did not appear to impact protein expression. In conclusion, prenatal tobacco use is associated with altered expression of multiple placental transporters which differs by fetal sex. As transcript levels of multiple transporters were significantly correlated with tobacco use biomarkers, eliminating prenatal tobacco use should alleviate these changes.

Abstract Background Face-to-face tobacco cessation has had limited reach and efficacy in Alaska Native (AN) communities. We describe our two-phased approach to develop content for Connecting Alaska Native People to Quit Smoking, a Facebook group intervention to reduce barriers to evidence-based smoking cessation treatment for AN people in Alaska. Methods Phase 1 included semi-structured telephone interviews with 30 AN people who smoke and ten stakeholders. They provided feedback on existing content from the Centers for Disease Control and Prevention Tips campaign and AN digital stories. Phase 2 included an online survey with a new group of 40 AN smokers who provided feedback on existing content via a measure of perceived effectiveness and cultural relevance. Results Phase I results revealed participants evaluated content based upon story strength, relevance to AN culture, emotional appeal, relatability to AN people, and favorite video. No single posting was rated highly across all themes. All perceived effectiveness (PE) and cultural relevance median scores fell between 3.5 and 4.4 (range 1–5). PE scores varied across participant demographic groups. Conclusions Content embodying characteristics perceived to be most appealing, effective, and culturally relevant were selected for the private Facebook group content library with refinements made to incorporate images of AN people engaged in AN activities. PE scores indicate a need for a wide variety of content that moderators could pull from when conducting the intervention. Implications Social media content targeting specific population sectors, such as American Indian/AN people for tobacco cessation needs to be culturally tailored. Our approach provides a model others can follow to determine what is appealing, relevant, and effective messaging. Clinical Trial Registration NCT 03645941.

Prior research explored reasons for tobacco use among pregnant Alaska Native (AN) women but did not address the postpartum period. This study followed up with AN women one to three years postpartum who had participated in a prenatal smoking cessation intervention study (Motivate Alaska Women (MAW) Phase 3) and had consented to be re-contacted for future studies. Of 47 eligible women, 32 (68%) participated. A semi-structured phone interview was conducted a mean of 2.0 years after delivery (range 1.6–2.8). Measures assessed self-reported tobacco use status in the 12 months after delivery, at 12 months postpartum, and at the time of the interview; reasons for maintaining abstinence, continued use, or relapse; and included the Perceived Stress Scale (PSS) and Negative Affect (NA) scale. Content analysis was used to generate themes from open-ended response items. Tobacco use was reported by 23 women (72%) at delivery, 30 (94%) within the 12 months after delivery, 27 (84%) at 12 months postpartum, and 29 (91%) at the time of the interview. Among nine women not using tobacco at delivery, seven (78%) relapsed during the 12 months after delivery. Of the 29 current tobacco users, 28 (97%) smoked cigarettes. Twenty-seven participants (84%) reported stress and 15 (52%) indicated addiction as reasons for continuing, starting, or resuming tobacco use. Types of stressors were related to parenting and traumatic experiences. Among current tobacco users, mean NA score (18.7) was significantly higher (p = 0.01) than the normative mean (14.8), but no differences were detected for PSS score. In this sample of AN women, postpartum tobacco use was highly prevalent, and stress was a primary reason that women endorsed for using tobacco. These preliminary results have several practice and research implications for exploring ways to support non-tobacco use among postpartum AN women.